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1.
Sci Rep ; 10(1): 12644, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32724089

RESUMO

Tendons are specialized tissues composed primarily of load-responsive fibroblasts (tenocytes) embedded in a collagen-rich extracellular matrix. Habitual mechanical loading or targeted exercise causes tendon cells to increase the stiffness of the extracellular matrix; this adaptation may occur in part through collagen synthesis or remodeling. Integrins are likely to play an important role in transmitting mechanical stimuli from the extracellular matrix to tendon cells, thereby triggering cell signaling pathways which lead to adaptive regulation of mRNA translation and protein synthesis. In this study, we discovered that mechanical stimulation of integrin ß1 leads to the phosphorylation of AKT, an event which required the presence of integrin-linked kinase (ILK). Repetitive stretching of tendon cells activates the AKT and mTOR pathways, which in turn regulates mRNA translation and collagen expression. These results support a model in which integrins are an upstream component of the mechanosensory cellular apparatus, regulating fundamental tendon cell functions relevant to exercise-induced adaptation and mechanotherapy.

2.
Am J Sports Med ; 48(2): 285-297, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31940222

RESUMO

BACKGROUND: Persistent anterolateral rotatory laxity after anterior cruciate ligament (ACL) reconstruction (ACLR) has been correlated with poor clinical outcomes and graft failure. HYPOTHESIS: We hypothesized that a single-bundle, hamstring ACLR in combination with a lateral extra-articular tenodesis (LET) would reduce the risk of ACLR failure in young, active individuals. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: This is a multicenter, prospective, randomized clinical trial comparing a single-bundle, hamstring tendon ACLR with or without LET performed using a strip of iliotibial band. Patients 25 years or younger with an ACL-deficient knee were included and also had to meet at least 2 of the following 3 criteria: (1) grade 2 pivot shift or greater, (2) a desire to return to high-risk/pivoting sports, (3) and generalized ligamentous laxity (GLL). The primary outcome was ACLR clinical failure, a composite measure of rotatory laxity or a graft rupture. Secondary outcome measures included the P4 pain scale, Marx Activity Rating Scale, Knee injury Osteoarthritis and Outcome Score (KOOS), International Knee Documentation Committee score, and ACL Quality of Life Questionnaire. Patients were reviewed at 3, 6, 12, and 24 months postoperatively. RESULTS: A total of 618 patients (297 males; 48%) with a mean age of 18.9 years (range, 14-25 years) were randomized. A total of 436 (87.9%) patients presented preoperatively with high-grade rotatory laxity (grade 2 pivot shift or greater), and 215 (42.1%) were diagnosed as having GLL. There were 18 patients lost to follow-up and 11 who withdrew (~5%). In the ACLR group, 120/298 (40%) patients sustained the primary outcome of clinical failure, compared with 72/291 (25%) in the ACLR+LET group (relative risk reduction [RRR], 0.38; 95% CI, 0.21-0.52; P < .0001). A total of 45 patients experienced graft rupture, 34/298 (11%) in the ACLR group compared with 11/291 (4%) in the ACL+LET group (RRR, 0.67; 95% CI, 0.36-0.83; P < .001). The number needed to treat with LET to prevent 1 patient from graft rupture was 14.3 over the first 2 postoperative years. At 3 months, patients in the ACLR group had less pain as measured by the P4 (P = .003) and KOOS (P = .007), with KOOS pain persisting in favor of the ACLR group to 6 months (P = .02). No clinically important differences in patient-reported outcome measures were found between groups at other time points. The level of sports activity was similar between groups at 2 years after surgery, as measured by the Marx Activity Rating Scale (P = .11). CONCLUSION: The addition of LET to a single-bundle hamstring tendon autograft ACLR in young patients at high risk of failure results in a statistically significant, clinically relevant reduction in graft rupture and persistent rotatory laxity at 2 years after surgery. REGISTRATION: NCT02018354 ( ClinicalTrials.gov identifier).

3.
Clin Biomech (Bristol, Avon) ; 51: 17-25, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29154178

RESUMO

BACKGROUND: High tibial osteotomy is a surgical procedure to treat medial compartment osteoarthritis in varus knees. The reported success rates of the procedure are inconsistent, which may be due to sagittal plane alignment of the osteotomy. The objective of this study was to determine the effect of changing tibial slope, for a range of tibial wedge angles in high tibial osteotomy, on knee joint contact pressure location and kinematics during continuous loaded flexion/extension. METHODS: Seven cadaveric knee specimens were cycled through flexion and extension in an Oxford knee-loading rig. The osteotomy on each specimen was adjusted to seven clinically relevant wedge and slope combinations. We used pressure sensors to determine the position of the centre of pressure in each compartment of the tibial plateau and infrared motion capture markers to determine tibiofemoral and patellofemoral kinematics. FINDINGS: In early knee flexion, a 5° increase in tibial slope shifted the centre of pressure in the medial compartment anteriorly by 4.5mm (P≤0.001), (from the neutral slope/wedge position). Increasing the tibial slope also resulted in the tibia translating anteriorly (P≤0.001). INTERPRETATION: Changes to the tibial slope during high tibial osteotomy for all tested wedge angles shifted the centre of pressure in both the medial and lateral compartments substantially and altered knee kinematics. Tibial slope should be controlled during high tibial osteotomy to prevent unwanted changes in tibial plateau contact loads.


Assuntos
Articulação do Joelho/fisiopatologia , Osteoartrite do Joelho/cirurgia , Osteotomia/métodos , Tíbia/cirurgia , Idoso , Fenômenos Biomecânicos , Feminino , Humanos , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/fisiopatologia , Pressão , Amplitude de Movimento Articular/fisiologia , Rotação , Tíbia/fisiopatologia
5.
Med Sci Sports Exerc ; 49(9): 1769-1777, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28398948

RESUMO

PURPOSE: Angiopoietin-like 4 (ANGPTL4) is known to play a variety of roles in the response to exercise, and more recently has been shown to enhance the healing of tendon, a fibrous load-bearing tissue required for efficient movement. The objective of the current study was to further explore the mechanisms of ANGPTL4's effect on tendon cells using a gene array approach. METHODS: Human tendon fibroblasts were treated with recANGPTL4 and their global transcriptome response analyzed after 4 and 24 h. We also conducted functional studies using tendon fibroblasts derived from human subjects, cultured in the presence or absence of applied cyclic stretch and/or siRNA for ANGPTL4, and as confirmation we also used tendon cells from wild type (ANGPTL4 +/+) or knockout (ANGPTL4-/-) mice. RESULTS: The leading functions of ANGPTL4 predicted by the resulting pathway analysis were cell movement and proliferation. The experiments demonstrated that ANGPTL4 significantly enhanced tendon cell proliferation and the cell cycle progression, as well as adhesion and migration. CONCLUSION: Taken together, these findings provide novel molecular insights into the effect of ANGPTL4, a multifunctional protein that regulates the physiological response to exercise, on fundamental tendon cell functions.


Assuntos
Proteína 4 Semelhante a Angiopoietina/farmacologia , Exercício Físico/fisiologia , Fibroblastos/efeitos dos fármacos , Traumatismos dos Tendões/fisiopatologia , Tendões/citologia , Cicatrização/fisiologia , Proteína 4 Semelhante a Angiopoietina/fisiologia , Animais , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Células Cultivadas/efeitos dos fármacos , Humanos , Camundongos , Camundongos Knockout , Análise Serial de Tecidos
7.
J Physiol ; 594(11): 2971-83, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-26670924

RESUMO

KEY POINTS: Angiopoietin-like 4 (ANGPTL4) modulates tendon neovascularization. Cyclic loading stimulates the activity of transforming growth factor-ß and hypoxia-inducible factor 1α and thereby increases the expression and release of ANGPTL4 from human tendon cells. Targeting ANGPTL4 and its regulatory pathways is a potential avenue for regulating tendon vascularization to improve tendon healing or adaptation. ABSTRACT: The mechanisms that regulate angiogenic activity in injured or mechanically loaded tendons are poorly understood. The present study examined the potential role of angiopoietin-like 4 (ANGPTL4) in the angiogenic response of tendons subjected to repetitive mechanical loading or injury. Cyclic stretching of human tendon fibroblasts stimulated the expression and release of ANGPTL4 protein via transforming growth factor-ß (TGF-ß) and hypoxia-inducible factor 1α (HIF-1α) signalling, and the released ANGPTL4 was pro-angiogenic. Angiogenic activity was increased following ANGPTL4 injection into mouse patellar tendons, whereas the patellar tendons of ANGPTL4 knockout mice displayed reduced angiogenesis following injury. In human rotator cuff tendons, the expression of ANGPTL4 was correlated with the density of tendon endothelial cells. To our knowledge, this is the first study characterizing a role of ANGPTL4 in the tendon. ANGPTL4 may assist in the regulation of vascularity in the injured or mechanically loaded tendon. TGF-ß and HIF-1α comprise two signalling pathways that modulate the expression of ANGPTL4 by mechanically stimulated tendon fibroblasts and, in the future, these could be manipulated to influence tendon healing or adaptation.


Assuntos
Angiopoietinas/biossíntese , Fibroblastos/metabolismo , Neovascularização Fisiológica/fisiologia , Tendões/metabolismo , Suporte de Carga/fisiologia , Aminoácidos Dicarboxílicos/farmacologia , Proteína 4 Semelhante a Angiopoietina , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Células HeLa , Células Endoteliais da Veia Umbilical Humana , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neovascularização Fisiológica/efeitos dos fármacos , Tendões/efeitos dos fármacos
8.
Am J Sports Med ; 43(10): 2469-80, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26260465

RESUMO

BACKGROUND: Current cartilage repair histological scoring systems are unable to explain the relationship between collagen type II deposition and overall repair quality. PURPOSE/HYPOTHESIS: The purpose of this study was to develop a novel zonal collagen type (ZCT) 5-point scoring system to measure chondroinduction in human clinical biopsy specimens collected after marrow stimulation. The hypothesis was that the ZCT scores would correlate with the International Cartilage Repair Society-II (ICRS-II) overall histological repair assessment score and glycosaminoglycan (GAG) content. STUDY DESIGN: Descriptive laboratory study. METHODS: After optimizing safranin O staining for GAG and immunostaining for human collagen type II and type I (Col2 and Col1, respectively), serial sections from clinical osteochondral repair biopsy specimens (13 months after microfracture or microfracture with BST-CarGel; n = 39 patients) were stained and 3 blinded readers performed histomorphometry for percentage of staining, ICRS-II histological scoring, polarized light microscopy (PLM) scoring, and 5-point ZCT scoring based on tidemark morphology, zonal distribution of Col2 and Col1, and Col1 percentage stain. Because 1 biopsy specimen was missing bone, 38 biopsy specimens were evaluated for ICRS-II, PLM, and ZCT scores. RESULTS: Chondroinduction was identified in 21 biopsy specimens as a Col2 matrix fused to bone that spanned the deep-middle-superficial zones ("full-thickness hyaline repair"), deep-middle zones, or deep zone ("stalled hyaline") that was covered with a variable-thickness Col1-positive matrix, and was scored, respectively, as ZCT = 1 (n = 4 biopsy specimens), ZCT = 2 (n = 6) and ZCT = 3 (n = 11). Other biopsy specimens (n = 17) were fibrocartilage (n = 9; ZCT = 4), fibrous tissue (n = 4, ZCT = 5), or non-marrow derived (n = 4; ZCT = 0). Non-marrow derived tissue had a mean mature tidemark score of 84 out of 100 versus a regenerating tidemark score of 24 for all other biopsy specimens (P = .005). Both "stalled hyaline" repair and fibrocartilage had the same mean Col2 percentage stain; however, fibrocartilage was distinguished by heavy Col1 deposits in the deep zone, a 2-fold higher mean Col1 percentage stain (P = .001), and lower surface integrity (P = .03). ZCT scores correlated with GAG content and the ICRS-II overall assessment score, especially when combined with the PLM score for collagen organization (R = 0.82). Histological scores of the deep zone strongly predicted the ICRS-II overall assessment score (R = 0.99). CONCLUSION: The ICRS-II overall repair assessment score and GAG content correlated with the extent of Col2 deposition free of fibrosis in the deep/middle zone rather than bulk accumulation of Col2. CLINICAL RELEVANCE: Biopsy tissue from the BST-CarGel randomized clinical trial (microfracture without and with BST-CarGel, as treatment groups were not unblinded) showed regenerated tissue consistent with a chondroinduction mechanism in at least half of the treated lesions.


Assuntos
Biópsia/métodos , Cartilagem Articular/patologia , Colágeno/metabolismo , Fraturas Ósseas/patologia , Glicosaminoglicanos/metabolismo , Traumatismos do Joelho/patologia , Adolescente , Adulto , Cartilagem Articular/lesões , Cartilagem Articular/metabolismo , Feminino , Fibrocartilagem/metabolismo , Fibrocartilagem/patologia , Fluconazol , Fraturas Ósseas/metabolismo , Humanos , Traumatismos do Joelho/metabolismo , Masculino , Pessoa de Meia-Idade , Cicatrização , Adulto Jovem
9.
Knee ; 22(3): 156-62, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25715920

RESUMO

PURPOSE: The aims of this study are to determine how opening-wedge high tibial osteotomy (HTO) affects cartilage health in the tibiofemoral (TF) joint and patella, and to explore relationships between TF and patellofemoral (PF) joint kinematics and cartilage health in HTO. METHODS: 14 knees (13 subjects) with medial TF osteoarthritis (OA) were examined before HTO and 6 and 12 months after HTO using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) to evaluate cartilage health at the TF joint and patella. They were also examined using a validated 3D MR knee kinematics measurement to obtain 11 rotations and translations at both TF and PF joints. RESULTS: No statistically significant differences in overall TF or patellar dGEMRIC score were found at 6 or 12 months after HTO. However three subjects had large decreases (mean 105 ms) in TF dGEMRIC at 6 months that recovered at 12 months. Kinematics for these subjects were compared to subjects who did not have decreases in TF dGEMRIC at 6 months (n=5). Differences were observed between groups with HTO in anterior and proximal tibial translation (mean differences 3.05 mm and 1.35 mm), and patellar flexion (mean difference 3.65°). These changes were consistent between 6 and 12 months, despite recovery of TF dGEMRIC values. CONCLUSIONS: We did not find significant differences in TF or patellar dGEMRIC before and after HTO with all subjects, however there were differences in kinematics between subjects who had a decrease in TF dGEMRIC at 6 months and those who did not. This suggests a link between joint kinematics and cartilage health in HTO. CLINICAL RELEVANCE: The effect of opening-wedge high tibial osteotomy on cartilage GAG concentration may be linked to specific changes in knee kinematics following surgery.


Assuntos
Cartilagem Articular/patologia , Osteoartrite do Joelho/cirurgia , Osteotomia/métodos , Articulação Patelofemoral/cirurgia , Amplitude de Movimento Articular , Tíbia/cirurgia , Adulto , Fenômenos Biomecânicos , Seguimentos , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/fisiopatologia , Articulação Patelofemoral/fisiopatologia
10.
J Orthop Res ; 33(1): 9-16, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25293783

RESUMO

Mast cells and fibroblasts are two key players involved in many fibrotic and degenerative disorders. In the present study we examined the nature of binding interactions between human mast cells and tendon fibroblasts (tenocytes). In the mast cell-fibroblast co-culture model, mast cells were shown to spontaneously bind to tenocytes, in a process that was partially mediated by α5ß1 integrin receptors. The same receptors on mast cells significantly mediated binding of these cells to tissue culture plates in the presence of tenocyte-conditioned media; the tenocyte-derived fibronectin in the media was shown to also play a major role in these binding activities. Upon binding to tenocytes or tissue culture plates, mast cells acquired an elongated phenotype, which was dependent on α5ß1 integrin and tenocyte fibronectin. Additionally, tenocyte-derived fibronectin significantly enhanced mRNA expression of the adhesion molecule, THY1, by mast cells. Our data suggests that α5ß1 integrin mediates binding of mast cells to human tenocyte and to tenocyte-derived ECM proteins, in particular fibronectin.


Assuntos
Comunicação Celular/fisiologia , Fibroblastos/citologia , Mastócitos/citologia , Tendões/citologia , Adesão Celular/fisiologia , Linhagem Celular , Células Cultivadas , Técnicas de Cocultura , Matriz Extracelular/fisiologia , Feminino , Fibroblastos/fisiologia , Fibronectinas/fisiologia , Humanos , Técnicas In Vitro , Integrina alfa5beta1/fisiologia , Masculino , Mastócitos/fisiologia , Proteínas Proto-Oncogênicas c-kit/fisiologia , Tendões/fisiologia , Antígenos Thy-1/fisiologia
11.
Rheumatology (Oxford) ; 54(2): 318-23, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25150176

RESUMO

OBJECTIVE: Glucocorticoid injections are used by rheumatologists to treat chronic tendinopathy. Surprisingly, the mechanisms by which corticosteroids induce pain relief in this condition have not been investigated. Previous studies have shown local substance P (SP) levels to be correlated with tendon pain and tissue pathology. The objective of this study was to determine whether SP production in human tenocytes is modulated by exposure to dexamethasone. METHODS: Human tendon fibroblasts were cultured in the presence or absence of dexamethasone (1-400 nM), an inhibitor of the glucocorticoid receptor, RU486, recombinant TGF-ß (2.5 or 5.0 ng/ml) or an inhibitor of the TGF-ß receptor (A83.01), recombinant human IL-1ß and IL-6. Expression levels of the genes encoding for SP (TAC1) and its preferred receptor (NK1R), IL-1α, IL-1ß and IL-6 were determined with quantitative PCR and protein levels of SP were examined by EIA and western blot. RESULTS: Exposure of human tendon cells to dexamethasone resulted in a time-dependent reduction of mRNA for SP in both hamstrings and Achilles tenocytes, whereas NK1R was unaffected. The reduction of SP mRNA was dependent on signalling through the glucocorticoid receptor. SP protein was substantially decreased by dexamethasone. Dexamethasone also prevented induction of SP by IL-1ß and by cyclic mechanical loading. CONCLUSION: This study demonstrates that dexamethasone treatment of human tendon fibroblasts reduces the expression of SP through a glucocorticoid receptor-dependent pathway. Drugs interfering with SP signalling could be a future target in the treatment of tendinopathy.


Assuntos
Dexametasona/farmacologia , Glucocorticoides/farmacologia , Substância P/metabolismo , Tendões/metabolismo , Tendão do Calcâneo/metabolismo , Adulto , Células Cultivadas , Regulação para Baixo , Feminino , Fibroblastos/metabolismo , Expressão Gênica , Voluntários Saudáveis , Humanos , Técnicas In Vitro , Masculino , Receptores da Neurocinina-1/metabolismo , Adulto Jovem
12.
BMC Musculoskelet Disord ; 15: 386, 2014 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-25414072

RESUMO

BACKGROUND: Mechanical stimulation (e.g. slow heavy loading) has proven beneficial in the rehabilitation of chronic tendinopathy, however the optimal parameters of stimulation have not been experimentally determined. In this study of mechanically stimulated human tenocytes, the influence of rest insertion and cycle number on (1) the protein and mRNA levels of type I and III collagen; (2) the mRNA levels of transforming growth factor beta (TGFB1) and scleraxis (SCXA); and (3) tenocyte morphology, were assessed. METHODS: Human hamstring tenocytes were mechanically stimulated using a Flexcell® system. The stimulation regimens were 1) continuous and 2) rest-inserted cyclic equiaxial strain at a frequency of 0.1 Hz for 100 or 1000 cycles. Data were normalized to unstimulated (non-stretched) control groups for every experimental condition. qPCR was performed to determine relative mRNA levels and quantitative immunocytochemistry image analysis was used to assess protein levels and cell morphology. RESULTS: Collagen type I mRNA level and pro-collagen protein levels were higher in tenocytes that were subjected to rest-inserted mechanical stimulation, compared to continuous stretching (p<0.05). Rest insertion and increased cycle number also had significant positive effects on the levels of mRNA for TGFB1 and SCXA (p<0.05). There was no direct relation between cell morphology and gene expression, however mechanical stimulation, overall, induced a metabolically active tenocyte phenotype as evidenced by cells that on average demonstrated a decreased major-minor axis ratio (p<0.05) with greater branching (p<0.01). CONCLUSIONS: The incorporation of rest periods in a mechanical stretching regimen results in greater collagen type I synthesis. This knowledge may be beneficial in refining rehabilitation protocols for tendon injury.


Assuntos
Tamanho Celular , Colágeno Tipo I/biossíntese , Estresse Mecânico , Tendões/citologia , Tendões/metabolismo , Células Cultivadas , Humanos , RNA Mensageiro/biossíntese , Fatores de Tempo
13.
Injury ; 45(10): 1549-53, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24893919

RESUMO

BACKGROUND: Operative fixation of displaced, mid-shaft clavicle fractures has become an increasingly common practice. With this emerging trend, data describing patient outcomes with longer follow-up are necessary. PATIENTS AND METHODS: We retrospectively reviewed the medical records of subjects treated with plate fixation for displaced mid-shaft clavicle fractures from 2003 to 2009 at a Level I trauma hospital. All subjects were greater than 12 months post-index surgery. Treatment involved ORIF with either a low-contact dynamic compression plate (LCDC) or a contoured plate (pre-contoured or pelvic reconstruction plate). Our primary outcome was reoperation for any indication. RESULTS: 143 subjects were included. The mean age was 36 ± 14 years and the mean time to reoperation or chart review was 33 months. Contoured plates were used in 64% of cases and LCDC plates were used in the remaining subjects. Twenty-nine subjects (20%) underwent reoperation: 23.5% of subjects treated with LCDC plates and 18.5% of subjects treated with contoured plates (p=0.52). Indications for reoperation included implant irritation (n=25), implant failure (n=2), and non-union (n=2). There was near statistically significant association with reoperation and female gender (p=0.05) but no association between reoperation and age (p=0.14), fracture class (p=0.53), plate type (p=0.49), or plate location (p=0.93). The mean QuickDASH score for the population surveyed was 8.8 (5.5-12.1; 95% CI) with near statistically significant and clinically relevant difference between those considering reoperation and those not 22.3 (8.6-36.0; 95% CI) versus 6.7 (3.6-9.8; 95% CI). CONCLUSIONS: This study represents a large series of displaced clavicle fractures treated with open reduction and plate fixation. Reoperation following plate fixation is relatively common, but primarily due to implant irritation. No difference in reoperation rates between plate types or location could be detected in our current sample size. Also, excellent functional outcomes continue to be observed several years after clavicle fracture fixation.


Assuntos
Clavícula/cirurgia , Fraturas Ósseas/cirurgia , Fraturas não Consolidadas/cirurgia , Adolescente , Adulto , Idoso , Placas Ósseas , Clavícula/lesões , Clavícula/fisiopatologia , Estética , Feminino , Seguimentos , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/estatística & dados numéricos , Fraturas Ósseas/complicações , Fraturas Ósseas/fisiopatologia , Fraturas não Consolidadas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente/estatística & dados numéricos , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento
14.
PLoS One ; 9(5): e97356, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24824595

RESUMO

Angiogenesis is associated with the tissue changes underlying chronic overuse tendinopathy. We hypothesized that repetitive, cyclic loading of human tendon cells would lead to increased expression and activity of angiogenic factors. We subjected isolated human tendon cells to overuse tensile loading using an in vitro model (1 Hz, 10% equibiaxial strain). We found that mechanically stimulated human tendon cells released factors that promoted in vitro proliferation and tube formation by human umbilical vein endothelial cells (HUVEC). In response to cyclic strain, there was a transient increase in the expression of several angiogenic genes including ANGPTL4, FGF-2, COX-2, SPHK1, TGF-alpha, VEGF-A and VEGF-C, with no change in anti-angiogenic genes (BAI1, SERPINF1, THBS1 and 2, TIMP1-3). Cyclic strain also resulted in the extracellular release of ANGPTL4 protein by tendon cells. Our study is the first report demonstrating the induction of ANGPTL4 mRNA and release of ANGPTL4 protein in response to cyclic strain. Tenocytes may contribute to the upregulation of angiogenesis during the development of overuse tendinopathy.


Assuntos
Indutores da Angiogênese/metabolismo , Transtornos Traumáticos Cumulativos/fisiopatologia , Regulação da Expressão Gênica/fisiologia , Estresse Fisiológico/fisiologia , Tendões/metabolismo , Análise de Variância , Proteína 4 Semelhante a Angiopoietina , Angiopoietinas/metabolismo , Fenômenos Biomecânicos , Western Blotting , Transtornos Traumáticos Cumulativos/metabolismo , Ciclo-Oxigenase 2/metabolismo , Primers do DNA/genética , Ensaio de Imunoadsorção Enzimática , Fator 2 de Crescimento de Fibroblastos/metabolismo , Citometria de Fluxo , Perfilação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Técnicas In Vitro , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Estimulação Física , Tendões/citologia , Fator de Crescimento Transformador alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator C de Crescimento do Endotélio Vascular/metabolismo
15.
Physiother Can ; 65(4): 358-63, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24396164

RESUMO

PURPOSE: To investigate the effectiveness of a physiotherapy triage service for orthopaedic surgery referrals from primary-care physicians. METHODS: A prospective, observational design was used with patients referred to an orthopaedic surgeon based out of two small urban centres in British Columbia. The level of agreement between the physiotherapist and surgeon was determined using a weighted kappa statistic (κw) with 95% CI. A patient satisfaction questionnaire was administered, and the surgical conversion rate (SCR) was calculated to assess the level of appropriate referrals. RESULTS: The analysis found substantial agreement (κw=0.77; 95% CI, 0.60-0.94) between surgeon and physiotherapist for surgical management decisions. All patients reported being "satisfied" or "very satisfied" with the overall care they received from the physiotherapist. The SCR of patients referred by the physiotherapist to the surgeon was 91%, versus 22% among patients referred by a general practitioner or emergency physician. CONCLUSION: More than three-fourths of patients referred by primary-care physicians did not need to see a surgeon and were able to be managed by an experienced orthopaedic physiotherapist. This triage model could have considerable impact on orthopaedic wait times in Canada by minimizing unnecessary referrals; the model could also promote timely and conservative management of non-surgical conditions by physiotherapists.

16.
Am J Sports Med ; 40(4): 808-14, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22374942

RESUMO

BACKGROUND: Knees undergoing revision anterior cruciate ligament (ACL) reconstruction typically have more intra-articular injuries than do knees undergoing primary reconstruction. HYPOTHESIS: Previous partial meniscectomy (PM) is associated with a higher rate of chondral lesions at revision ACL reconstruction, whereas previous meniscal repair (MR) is not associated with a higher rate of chondral lesions at revision ACL reconstruction, compared with knees undergoing revision ACL with no previous meniscal surgery. STUDY DESIGN: Cohort study (Prevalence); Level of evidence, 2. METHODS: Data from a multicenter cohort was reviewed to determine the history of prior meniscal surgery (PM/MR) and the presence of grade II/III/IV chondral lesions at revision ACL reconstruction. The association between previous meniscal surgery and the incidence of chondral lesions was examined. Patient age was included as a covariate to determine if surgery type contributes predictive information independent of patient age. RESULTS: The cohort included 725 ACL revision surgeries. Chondrosis was associated with patient age (P < .0001) and previous meniscal surgery (P < .0001). After adjusting for patient age, knees with previous PM were more likely to have chondrosis than knees with previous MR (P = .003) or no previous meniscal surgery (P < .0001). There was no difference between knees without previous meniscal surgery and knees with previous MR (P = .7). Previous partial meniscectomy was associated with a higher rate of chondrosis in the same compartment compared with knees without previous meniscal surgery (P < .0001) and knees with previous MR (P ≤ .03). CONCLUSION: The status of articular cartilage at the time of revision ACL reconstruction relates to previous meniscal surgery independent of the effect of patient age. Previous partial meniscectomy is associated with a higher incidence of articular cartilage lesions, whereas previous meniscal repair is not. Although this association may reflect underlying differences in the knee at the time of prior surgery, it does suggest that meniscal repair is preferable when possible at the time of ACL reconstruction.


Assuntos
Condroma/epidemiologia , Condroma/patologia , Meniscos Tibiais/cirurgia , Lesões do Menisco Tibial , Adolescente , Adulto , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Criança , Condroma/etiologia , Estudos de Coortes , Feminino , Humanos , Traumatismos do Joelho/patologia , Traumatismos do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estados Unidos/epidemiologia , Adulto Jovem
17.
J Orthop Trauma ; 24(4): 250-4, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20335760

RESUMO

OBJECTIVES: To assess the treatment preferences of orthopaedic surgeons for displaced three- and four-part proximal humerus fractures. DESIGN: Cross-sectional survey. SETTING: Academic and nonacademic institutions across Canada. PATIENTS/PARTICIPANTS: Members of the Canadian Orthopedic Trauma Society and the Joint Orthopedic Initiative for National Trials of the Shoulder. INTERVENTION: Mailed questionnaire requesting treatment preferences for eight clinical scenarios with differing patient age (45 or 68 years), patient activity level (active/healthy or frail/low demand), and fracture type (Neer III or IV). MAIN OUTCOME MEASUREMENTS: Treatment preference for each clinical scenario using a five-level ordinal scale. RESULTS: Thirty-six completed questionnaires were included in the analysis. Internal fixation, particularly with locking plates, was the preferred treatment for young patients regardless of fracture type or activity level. Treatment preferences for elderly patients demonstrated the least consensus. Hemiarthroplasty, locked plating, and nonoperative management all received high treatment preferences depending on the fracture type and activity level of the patient. CONCLUSIONS: This survey quantifies treatment preferences for a wide range of strategies used to manage displaced proximal humerus fractures. The results of this survey suggest that, despite consulting orthopaedic trauma and shoulder experts, a wide range of treatments appear acceptable for displaced fractures in the elderly. Prospective clinical trials are needed to guide effective treatment decisions for these patients.


Assuntos
Fixação Interna de Fraturas/estatística & dados numéricos , Traumatismo Múltiplo/epidemiologia , Traumatismo Múltiplo/cirurgia , Padrões de Prática Médica/estatística & dados numéricos , Fraturas do Ombro/epidemiologia , Fraturas do Ombro/cirurgia , Idoso , Canadá/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Clin J Sport Med ; 16(5): 453-4, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17016128
19.
Arthroscopy ; 22(8): 889-93, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16904589

RESUMO

PURPOSE: A significant proportion of surgeons use intra-articular drains after arthroscopic anterior cruciate ligament (ACL) reconstruction. The usual reason given to justify the use of a drain is to minimize patient pain and stiffness of the knee joint. The purpose of this study was to assess the validity of this approach. METHODS: In this study 118 consecutive ACL reconstruction patients were randomized to no drain or a postoperative intra-articular suction drain. Inclusion criteria included a successful ACL reconstruction via either 4-strand hamstrings or bone-patellar tendon-bone autograft as a graft source. The primary outcomes were defined as pain (assessed by pain scores and analgesic counts) and range of motion (ROM) (assessed by loss of flexion and extension compared with the nonoperative leg). An independent statistical analysis was performed. RESULTS: The 2 groups were comparable with respect to patient demographics, surgical findings, and procedures performed. There were no differences between the treatment groups for the primary outcomes of pain and ROM during the 8-week follow-up period. The study had adequate power to detect a clinically significant difference. Regarding the secondary outcomes, there was a difference in the grade of hemarthrosis between the groups at week 1 but not at week 4 or 8. However, the difference in subjective grade of hemarthrosis at 1 week did not have any effect on the primary outcomes of pain and ROM. During the study period, there were no complications in either group. CONCLUSIONS: The routine use of intra-articular drains after arthroscopic ACL surgery was not supported by this study. LEVEL OF EVIDENCE: Level II, randomized controlled trial without narrow confidence intervals.


Assuntos
Ligamento Cruzado Anterior/cirurgia , Artroscopia/efeitos adversos , Drenagem , Artropatias/prevenção & controle , Adulto , Lesões do Ligamento Cruzado Anterior , Artralgia/etiologia , Artralgia/prevenção & controle , Transplante Ósseo , Feminino , Humanos , Artropatias/etiologia , Masculino , Estudos Prospectivos , Amplitude de Movimento Articular , Tendões/transplante , Resultado do Tratamento
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